α‐Aminophosphonates as Potential PARP1 Inhibitors

Abstract

ADP-ribosyl transferase member 1 (PARP1) is primarily known for its involvement in signaling DNA damage repair mechanisms within a cell. PARP1 inhibitors are used currently for the management of breast cancer (BRCA) gene mutated breast and ovarian cancers. These current generation PARP1 inhibitors are non-selective for PARP1, over the PARP superfamily enzymes.Here we report on a novel class of PARP1 inhibitors, the αaminophosphonates. α-Αminophosphonates 1-23 were screened in silico for their binding interactions and tested for inhibitory activity against PARP1. α-Aminophosphonates 17 and 20 were identified as the most effective PARP1 inhibitors. They inhibited PARP1's activity, at 10 μM, by 63 � 3% and 56 � 3%, respectively.[a] Dr.

Catalyst‐ and Solvent‐Free Room Temperature Synthesis of α‐Aminophosphonates: Green Accomplishment of the Kabachnik–Fields Reaction

“…α‐Aminophosphonic acids and α‐aminophosphonates are important representatives of organophosphorus compounds. They possess a wide range of biological activities acting as enzyme inhibitors, [1] antibiotics, [2] anticancer agents, [3] herbicides, [4] and plant growth regulators [5] . Two prominent representatives of this family of compounds are shown in Figure 1: nitrosourea alkylating agent fotemustine ( 1 ) is a drug for the treatment of metastatic melanoma and brain cancer, and the novel antiviral agent dufulin ( 2 ), a pesticide activating the systemic acquired resistance of plants [6,7] …”

Primary amines as new carbonyl surrogate in Kabachnik‐fields reaction: A new metal free one pot approach to synthesize α‐Aminophosphonates in water

“…α-Aminophosphonates form an important group of organophosphorus compounds, because of their similar structure with α-amino acids, these compounds shows broad range of biological, industrial and agricultural applications (Figure 1). [18][19][20][21][22][23][24][25][26][27][28] Pudovik reaction, [29] Kabachnik-fields reaction, [30] Michaelis-Arbuzov [31] and Michaelis-Baker [32] serve as some of the classical approaches to synthesis α-aminophosphonates (Scheme 1). Among these Kabachnik-fields reaction serves as a useful, mild and economical route to access aminophosphonates.…”